Pulmonary alveolar proteinosis (PAP) is a rare disease marked by accumulation of proteins and lipids in the narrow gas-exchange pockets of the lungs, leading to respiratory failure. PAP is an autoimmune disorder in which patients generate antibodies against a normal protein found in the circulation (GM-CSF), which is a critical modulator of macrophage development. When circulating macrophages are impaired, they are unable to reach the lungs and clear the accumulated proteins and lipids. The goal of this project is to develop inhaled GM-CSF as therapy for PAP. As GM-CSF is currently used as an intravenous treatment for other conditions, the U.S. Food and Drug Administration (FDA) has required the completion of a formal toxicology study to ensure safety before proceeding to further clinical trials in humans for PAP. A comprehensive project plan was developed by TRND and the lead collaborators at Cincinnati Children's Hospital. The team subsequently entered into collaboration with Genzyme Corporation, who are providing essential research materials to the partnership. TRND supported extensive preliminary primate toxicology and dosing studies necessary to demonstrate the safety of using inhaled GM-CSF, and completed formal Investigational New Drug (IND)-enabling toxicology studies. Once an IND application is cleared by the Food and Drug Administration, TRND will support clinical pharmacology and pharmacokinetic studies.